Polypeptide variants with altered effector function

Abstract

The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.

What is claimed is: 
     
       1. Isolated nucleic acid encoding a variant of a parent polypeptide comprising an Fc region, wherein the Fc region mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of human effector cells more effectively, or binds an Fc gamma receptor III (FcγRIII) with better affinity, than the parent polypeptide and wherein the Fc region comprises an amino acid modification at amino acid position 339 and does not comprise a modification of the lower hinge region wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat. 
     
     
       2. A vector comprising the nucleic acid of  claim 1 . 
     
     
       3. A host cell containing the vector of  claim 2 . 
     
     
       4. A method for producing a polypeptide variant comprising culturing the host cell of  claim 3  so that the nucleic acid is expressed. 
     
     
       5. The method of  claim 4  further comprising recovering the polypeptide variant from the host cell culture. 
     
     
       6. The nucleic acid of  claim 1  wherein the parent polypeptide is an antibody or an immunoadhesin. 
     
     
       7. The nucleic acid of  claim 6  wherein the parent polypeptide is an antibody. 
     
     
       8. The nucleic acid of  claim 1  wherein the parent polypeptide Fc region comprises a human IgG Fc region. 
     
     
       9. The nucleic acid of  claim 8  wherein the human IgG Fc region comprises a human IgG1, IgG2, IgG3 or IgG4 Fc region. 
     
     
       10. The nucleic acid method of  claim 1  wherein the variant mediates ADCC about 1.5 fold to about 100 fold more effectively than the parent polypeptide. 
     
     
       11. The nucleic acid of  claim 1  wherein the variant binds an FcγRIII with better affinity than the parent polypeptide. 
     
     
       12. The nucleic acid of  claim 11  wherein the variant further binds an FcγRII with worse affinity than the parent polypeptide. 
     
     
       13. The nucleic acid of  claim 1 , wherein the amino acid modification is A339T.